Spectrum of congenital heart disease in Nepal from 2002–2022: A systematic review and meta‐analysis

Abstract Background Congenital heart diseases are recognized as public health concerns worldwide and Nepal is no exception. This study aims to study congenital heart disease in Nepal on grounds of burden, commonest type, common presentations, and associated noncardiac anomalies so that its spectrum can be known for prompt diagnosis and adoption of screening protocols. Methods Relevant articles were searched in electronic databases using appropriate search terms and Boolean operators. Data were extracted in Excel and analyzed in Comprehensive Meta‐Analysis Software. The proportion was used as an effect measure and a fixed or random‐effect model was used as per the heterogeneity. Forest plots were used to give visual feedback. Results A total of nine studies were included in the qualitative and quantitative synthesis after a rigorous screening of imported studies. The prevalence of congenital heart disease was 0.7% (Proportion: 0.007; CI: 0.001–0.035; I2: 99.263%). The burden of atrial septal defect was 32.1%, ventricular septal defect was 31.1%, patent ductus arteriosus was 12.6% and Tetralogy of Fallot was 7.3%. The most common presentations were respiratory tract infection (54.7%), developmental delay (49.8%), difficulty in breathing (44.5%), failure to thrive (17.1%), and cyanosis (15.9%). Conclusions The prevalence of congenital heart disease in Nepal was 0.7% and the frequency of male patients was higher. The atrial septal defect was the commonest on the whole, while, Tetralogy of Fallot was the commonest among cyanotic variety. Respiratory tract infection was frequently seen at presentation and the most commonly associated noncardiac anomaly was the cleft palate.

genital heart disease" OR CHD OR "cyanotic heart disease" OR "acyanotic heart disease") AND (prevalence OR pattern OR spectrum) AND (Nepal). A time filter was used to search articles from the year 2002 to October, 2022. Details of the search and the results obtained from each database is available in Supporting Information: File 1.

| Inclusion criteria and exclusion criteria
This study intended to include all published articles (except for editorial, review articles, viewpoints, and commentaries) that have reported data on CHD of patients below 18 years of age, in Nepal.

| Study selection
All the relevant studies were imported to Covidence 8 and screening was done by two independent authors. Any conflicts that rose were resolved by the third reviewer. The role of the primary screener and conflict resolver were exchanged in the title-and-abstract screening phase and full-text screening phase.

| Data curation
A data collection tool was prepared in Excel and the same tool was used to extract data from included nine studies. The data extracted in Excel was peer-reviewed for correction of mistakes and refinement of the data. The data collection tool contained headings like author/s, study year, study design, study center, study address, sample size, study Population, total CHD patients, type of cardiac defect, presenting complaints, and associated noncardiac anomaly. While taking the data of the type of cardiac lesion from studies, the frequency of cardiac defects given in combination with noncardiac anomaly (like ASD + hernia) was treated as isolated cardiac lesions, whereas cardiac defects given in combination with other cardiac anomalies (like ASD + VSD) were given respective separate heading during data curation.

| Data synthesis
Statistical analysis was performed by using Comprehensive Meta-Analysis Software (CMA) version 3. 9 Proportion was used as the effect measure, I 2 test was used for heterogeneity, and fixed or random-effect model was used as per the heterogeneity. 10 Forest plot was used to give visual feedback.

| Risk of bias assessment
Risk of bias assessment of the individual study was performed using the Joanna Briggs Institute (JBI) critical appraisal tool. 11 Assessment of bias is shown in Table 1

| Qualitative synthesis
Summary of the details of the included studies are shown in Table 2.

| Prevalence of CHD
Pooling data using a random effect model from five studies reporting the total sample population and the total number of CHD cases, the prevalence was found to be 0.7% (Proportion: 0.007; CI: 0.001-0.035; I 2 : 99.263%) ( Figure 2). Sensitivity analysis of the prevalence of CHD was carried out by excluding individual studies, which showed no significant differences in the result, details given in  (Figure 3).

| Ventricular septal defect among CHD
Among the nine studies reporting the data of VSD, pooling of data using random effect model showed that 31.1% (Proportion: 0.311; CI: 0.234-0.400; I 2 : 81.152%) among CHD cases are of VSD ( Figure 4).

| Patent ductus arteriosus among CHD
Among studies reporting PDA cases, pooling of the data from seven studies data using fixed effect model showed the burden of PDA to be 12.6% (Proportion: 0.126; CI: 0.093-0.169; I 2 : 46.593%) ( Figure 5).

| Common presenting complaints
The most common presenting symptoms were found to be respiratory tract infection, developmental delay, difficult breathing, failure to thrive, and cyanosis in decreasing order. Details are mentioned in Table 3 and forest plots are given in Supporting Information: File 2.

| DISCUSSION
Congenital heart disease poses a great risk of morbidity/mortality and the entity is frequently encountered in the community. The present study, with pediatric age-group as study population, quantified prevalence of congenital heart disease in Nepal to be 0.7% (7 per 1000 individuals), by using data from nine different studies done across various regions of the country. Need for this study became crucial as there was no meta-analysis data that could be representative for the nation. Nepal is one of the lower-middle-income countries (LMIC) and can offer only the bare minimum to the citizens in the health sector. In such conditions, screening and reporting of the cases are not optimal. The burden of CHD that has been quantified in various studies is not the ground reality, and this can be said as the institutional delivery rate in Nepal is just 58% and the burden of CHD in the neighboring countries (India-1.01% and China-1.65%) and the whole Asia (0.93%) is more. [21][22][23][24] This speculation can only be accepted or discarded after thorough and extensive further study.
Among the categories of congenital structural abnormality of heart, acyanotic or noncyanotic CHD are the most common ones worldwide 24 and the findings of our study is in line with it. Ventricular septal defect is encountered as the most common one, however, this study found that

| CONCLUSION
The prevalence of congenital heart disease in Nepal was 7 per 1000 individuals in pediatric age group and the frequency of males was higher compared to females. Noncyanotic heart disease was more common, the atrial septal defect being the commonest of all, while Tetralogy of Fallot was commonest among cyanotic heart disease.
CHD should also be in the minds of healthcare providers when patients present with respiratory infection and cleft palate as these are more common than cyanosis. Also, cost-effective screening protocols are warranted to avoid delays in diagnosis and intervention.

ACKNOWLEDGMENTS
We are pleased to acknowledge our seniors and colleagues who helped us and motivated us.

CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
All the data curated in this study is available from the corresponding author on reasonable request.

TRANSPARENCY STATEMENT
The lead author Oshan Shrestha affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.